Based upon the demonstrated efficacy of male circumcision in reducing HIV acquisition in men,(1) the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommend offering circumcision to all men in countries with high HIV prevalence and low rates of male circumcision, regardless of known HIV status.(2) The effect of male circumcision on transmission of HIV to female partners is uncertain because observational studies have shown both reduced risk of transmission(3, 4) and no effect.(5) A clinical trial compared the incidence of HIV transmission among female partners of men randomly assigned to undergo and not to undergo circumcision. It found a short-term increased risk for partners when the men had sex before complete wound healing, but otherwise the incidence rates did not differ between the study arms.(6)

Objective

To examine the relation between male circumcision and women's risk of HIV infection

Setting

Seven sites in eastern Africa and seven sites in southern Africa

Study Design

The data used in this analysis come from a randomized clinical trial of the effectiveness of suppressive therapy against herpes simplex virus (HSV-2) at reducing HIV transmission among HIV-serodiscordant, heterosexual couples.

Participants

Participants were HIV-serodiscordant adult couples with at least three episodes of vaginal intercourse in the three months prior to enrollment and intent to remain together for at least 24 months. HIV-infected participants were required to have a minimum CD4 count of 250 cells/µL and no AIDS-defining conditions.

Outcome

HIV infection and predictors of seroconversion

Methods

HIV-infected participants were seen monthly for receipt of drug/placebo and for behavioral and clinical assessment. Persons who met the national standards for initiation of antiretroviral therapy (ART) were referred to ART clinics. Determination of male circumcision status was made by physical examination at study enrollment. HIV-uninfected partners were seen quarterly, at which time they were tested for HIV.

Included in this analysis were couples in which the male partner was infected with HIV. Nine participants tested negative for HIV antibodies at enrollment, but results of later testing of the baseline specimen were positive for HIV RNA, indicating seroconversion near the time of enrollment. Because male circumcision was likely to be present at the time of seroconversion, these events were included as endpoints in the analysis. Genetic analysis was done to determine if the incident infection occurred within the partnership. Women who acquired infection outside of the partnership were censored at the time of seroconversion. Additional analyses censored women at the time the partners initiated ART.

Results

A total of 1096 couples were included in this analysis. The median age of female participants was 30 years and for their male partners was 37 years. The median duration of the partnership was four years and the frequency of sex between the partners in the month prior to enrollment was four times; 27% of couples reported unprotected sex during this time. Six women reported sex outside of the partnership in the month before enrollment.

There were 374 (34%) circumcised men, and characteristics among them were similar to those of the uncircumcised men, except that men from eastern compared with southern Africa were more likely to be circumcised. In addition, the female partners of circumcised men were older. The baseline sexual behavior and CD4 counts and viral load levels were similar between the two groups.

Median follow-up was 18 months but was shorter for partners of uncircumcised men (18 vs. 21 months, P=0.03). The number of sexual episodes decreased over time between both groups.

There were 64 seroconversions (incidence rate of 3.8 per 100 person-years) and 50 were genetically linked to the partner. Incidence of HIV was lower among partners of circumcised than uncircumcised men (2.72 per 100 person-years vs. 4.38 per 100 person-years, respectively) but this difference was not statistically significant (hazard ratio 0.62, 95% confidence interval: 0.35-1.10).
This difference held for both genetically linked and unlinked seroconversions and after adjustment for HIV viral load, use of ART, unprotected intercourse, and incident genital ulcer disease.

Conclusions

Male circumcision was associated with a reduction in HIV incidence that was not statistically significant.

Quality Rating

This was a high-quality study. The sample was representative, and exposed and unexposed groups were similar in terms of HIV risk other than circumcision. Follow-up time was adequate, although there was some difference between the two groups. The methods for assessing the exposure and outcome were adequate.

Programmatic Implications

Although there is biological plausibility for male circumcision having a protective effect against HIV transmission to female partners, there is no consistent evidence of it. As such, HIV prevention programs that offer circumcision must present it as an effective method of reducing rates of HIV infection in circumcised men and not as protection from HIV for women. There is, however, evidence of increased risk of transmission to women whose male partners resumed sexual activity after circumcision but prior to complete healing.(6) Men infected with HIV who undergo circumcision should be thoroughly counseled to abstain from intercourse until healing is complete.